Differential ligand-signaling network of CCL19/CCL21-CCR7 system

Abstract

Chemokine (C-C motif) receptor 7 (CCR7), a class A subtype G-Protein Coupled Receptor (GPCR), is involved in the migration, activation and survival of multiple cell types including dendritic cells, T cells, eosinophils, B cells, endothelial cells and different cancer cells. Together, CCR7 signaling system has been implicated in diverse biological processes such as lymph node homeostasis, T cell activation, immune tolerance, inflammatory response and cancer metastasis. CCL19 and CCL21, the two well-characterized CCR7 ligands, have been established to be differential in their signaling through CCR7 in multiple cell types. Although the differential ligand signaling through single receptor have been suggested for many receptors including GPCRs, there exists no resource or platform to analyse them globally. Here, first of its kind, we present the cell-type-specific differential signaling network of CCL19/CCL21-CCR7 system for effective visualization and differential analysis of chemokine/GPCR signaling.Database URL: http:// www. netpath. org/ pathways? path_ id= NetPath_ 46.

The Role of CCL21/CCR7 Chemokine Axis in Breast Cancer Progression

“…The pathways used by CCR7 to facilitate metastasis are not fully understood. It has been reported that CCR7 facilitates cancer progression by manipulating cancer cells' anoikis and mobility [82] as well as controlling the tumor microenvironment, including the inflammatory responses, immune tolerance and T cell activation [105,106]. Downstream potential signaling mediators of CCR7 have been reported to be associated with metastasis, such as ALDH3A2, AnXA6, EpCAM, and PVR [107].…”

Hypoxia modulates CCR7 expression in head and neck cancers

“…I CCL T consistent with reports from other laboratories that have shown CCL21 is better at inducing migration [40] and probably reflects the difference in the intracellular pathways activated by the two ligands. [41] In control experiments, the colon cell line DLD-1 and SW480 which express little CCR7, showed no increase in motility in the presence of CCL21 whilst CCR7 expressing prostate PC-3 cell line did (Figure 1D, 1E).…”

Adenovirus-Mediated CCR7 and BTLA Overexpression Enhances Immune Tolerance and Migration in Immature Dendritic Cells

“…CCR7 and its ligands are crucial for DC migration [23–25]. The receptor is rapidly upregulated in mature DCs to regulate their migration into the lymphatics via a CCL21 gradient and then to drain lymph nodes in response to CCL19/MIP-3 β [21].…”